The objectives of this proposal are to study the immuno-regulatory cells present in the small intestine which control gut immune responses to bacterial and dietary antigens. These studies are designed to investigate the hypothesis that as a normal consequence of the continuous exposure of gut lymphocytes to enteric antigens, down-regulation of mucosal immune response by suppressor cells occurs to minimize responses (e.g. potentially hypersensitivity reactions) to antigens of little or no pathogenic significance (e.g. the antigens of the autochthonous flora). To this end lymphocytes will be isolated from intestinal lamina propria, intestinal epithelium and Peyer's patches and their regulatory functions studied in vitro and in vivo. The response to three antigens will be studied: phosphorylcholine (a carbohydrate antigen found on some gut bacteria), sheep red blood cells, (which have antigens in common with some gut bacteria), and ovalbumin (an antigen to which mice should have little exposure). It will then be determined if mucosa and Peyer's patches of normal mice contain T and B cells primed to phosphorylcholine, and if after feeding ovalbumin and sheep red cells if it is possible to detect primed T and B cells in the intestinal wall. B cell priming to these antigens will be assessed by their ability to generate antibody responses when stimulated in vitro or after transfer into x-irradiated recipients. Exposure of mucosal T cells to enteric antigen may lead to either helper and/or suppressor cell priming. Therefore, as well as studying whole mucosal T-cell populations, lymphocytes will be separated into Lyt sub-populations by panning. Helper activity will be assessed by investigating the ability of Lyt 1+2.3-cells to augment antibody responses in T-cell depleted cultures. Suppressor activity will be assessed by adding Lyt 1-2.3+ lymphocytes to in vitro cultures which have been set up so that an antibody response should occur in the absence of suppressive activity. Particular attention will be paid to the role of the mucosal regulatory T-cells bearing Fc receptors for IgA. It is anticipated that these studies will yield information on the way the mucosal immune system responds to the wide array of antigens present in the gut. As such, this work will also help our understanding of diseases such as inflammatory bowel disease where abnormal immune reactions in the gut wall have been implicated as important in pathogenesis.